US EPA

799705 

Journal Article 

Abstract 

Could phthalate's reproductive toxicity be due to it's disruption of inter-sertoli tight junction in two-compartment sertoli cell culture? 

Zhang, Y; Liu, Z; Chen, BH 

2005 

Yes 

Birth Defects Research, Part A: Clinical and Molecular Teratology
ISSN: 1542-0752
EISSN: 1542-0760 

73 

5 

313 

English 

BCI:BCI200600403529 

PURPOSES: In recent years, phthalate was considered as an environmental endocrine disruptor, which could affect reproduction and development of organisms by disturbing hormone synthesis. Animal data suggested a broad spectrum of health outcomes associated with phthalate exposure including developmental toxicity (cleft palate, decreased pup weight, testicular damage), endocrine disruption (testicular toxicity, decreased sperm motility, decrease fertility, decreased milk synthesis), and carcinogenicity. The purpose of this paper is to study the mechanism of phthalates' reproductive toxicity on Sertoli cell of rat testis.

METHODS: Based on the twocompartment primary Sertoli cell culture model, the effects of phthalates (di-n-butyl phthalate, di-2-ethylhexyl phthalate, mono-butyl phthalate and mono-2-ethylhexyl phthalate) on the tight junction of rat Sertoli cells were studied by the methods of light microscope, transmission electron microscope, transepithelial electrical resistance assay and immunofluorescence localization.

RESULTS: The results of TER measurement across the Sertoli cell epithelia showed that phthalates could destroy the tight junctions between Sertoli cells and germ cells. The damages of Sertoli cells included the destroyed cell monolayer, the loss of ridge line, the decline of transepithelial electrical resistance and the decreased expression of correlated proteins of tight junction such as ZO-1, F-actin and Occludin. This might be one of the reasons of testis atropy, which was the most often observed damage in phthalate-treated rats.

CONCLUSIONS: Phthalates can destroy the tight junction of Sertoli cell. Transepithelial electrical resistance can be a sensitive biomarker of phthalate effects on rat testis. 

Rats; Animals; Male; Cells, Cultured; Sertoli Cells/ULTRASTRUCTURE/DRUG EFFECTS; Tight Junctions/ULTRASTRUCTURE/DRUG EFFECTS; Phthalic Acids/CHEMISTRY/TOXICITY; Microscopy, Electron, Scanning; NO CAS RN 

45th Annual Meeting of the Teratology Society 

St. Pete Beach, FL 

June 25-30, 2005